Vascular inflammation is a hallmark of vulnerable atherosclerotic plaques, at high-risk for causing acute clinical events. 18F-labeled fluorodeoxyglucose (18F-FDG) Positron Emission Tomography (PET) imaging in combination with computed tomography (CT) has emerged as an accurate, reliable and reproducible tool to quantify vascular inflammation in carotid, aorta and femoral arteries. Recently, novel PET tracers such as 18F- labeled sodium fluoride (18F-NaF) have been used to target many biological processes in atherosclerosis other than inflammation, including active micro-calcification, which appears to be an important marker of unstable atherosclerotic plaques. Use of PET to quantify inflammation in coronary arteries is challenging due to respiratory and cardiac motions, and the limited spatial resolution of PET. These challenges can be overcome by using motion and partial volume correction strategies that may require long and repeated scans. However the use of CT exposes the subject to X-ray radiation and is unsuitable for such long repeated scans as well as for longitudinal tracking of interventions. Recently, systems that combine PET and Magnetic Resonance Imaging (MRI) have become available that allow for simultaneous, co-registered PET and MRI acquisitions. MRI requires no ionizing radiation and produces high spatial and temporal resolution images with excellent soft tissue contrast. These characteristics are ideally suited to repeated, tomographic imaging for motion correction, repeated scans in longitudinal studies, improving partial volume error (PVE) correction of the PET data, and in providing complementary information about coronary plaque morphology. As part of this grant proposal, we will develop and test methodologies for motion correction using MRI to optimize coronary PET imaging using phantoms and in an in vivo setting (Aim 1). We will also examine strategies for partial volume corrections of PET data to improve coronary PET imaging (Aim 2). As the final Aim (Aim 3) of this proposal, we will use methodologies developed and optimized in Aims 1 and 2 to evaluate in vivo, combined MR/PET imaging of FDG and NaF uptake in the coronary arteries of individuals following an acute myocardial infarction to determine the ability of these techniques to discriminate between the culprit lesions responsible for the clinical event and a non-culprit vessel.